Coresistance to isoniazid and ethionamide maps to mycothiol biosynthetic genes in Mycobacterium bovis.
نویسندگان
چکیده
A search to identify new mechanisms of isoniazid resistance in Mycobacterium bovis led to the isolation of mutants defective in mycothiol biosynthesis due to mutations in genes coding for the glycosyltransferase (mshA) or the cysteine ligase (mshC). These mutants showed low-level resistance to isoniazid but were highly resistant to ethionamide. This study further illustrates that mutations in mycothiol biosynthesis genes may contribute to isoniazid or ethionamide resistance across mycobacterial species.
منابع مشابه
Mycothiol biosynthesis is essential for ethionamide susceptibility in Mycobacterium tuberculosis
Spontaneous mutants of Mycobacterium tuberculosis that were resistant to the anti-tuberculosis drugs ethionamide and isoniazid were isolated and found to map to mshA, a gene encoding the first enzyme involved in the biosynthesis of mycothiol, a major low-molecular-weight thiol in M. tuberculosis. Seven independent missense or frameshift mutations within mshA were identified and characterized. P...
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متن کاملinhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis.
Isoniazid (isonicotinic acid hydrazide, INH) is one of the most widely used antituberculosis drugs, yet its precise target of action on Mycobacterium tuberculosis is unknown. A missense mutation within the mycobacterial inhA gene was shown to confer resistance to both INH and ethionamide (ETH) in M. smegmatis and in M. bovis. The wild-type inhA gene also conferred INH and ETH resistance when tr...
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متن کاملEthA/R-Independent Killing of Mycobacterium tuberculosis by Ethionamide
Ethionamide (ETH) is part of the drug arsenal available to treat multi-drug resistant tuberculosis. The current paradigm of this pro-drug activation involves the mycobacterial enzyme EthA and the transcriptional repressor, EthR. However, several lines of evidence suggest the involvement of additional players. The ethA/R locus was deleted in Mycobacterium bovis BCG and three Mycobacterium tuberc...
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ورودعنوان ژورنال:
- Antimicrobial agents and chemotherapy
دوره 55 9 شماره
صفحات -
تاریخ انتشار 2011